The long term objective of this investigation is directed towards elucidating a potential mechanism whereby membrane-enzyme interactions may participate in the control of cell growth and proliferation. Major emphasis of these studies will focus on the "signal transduction-amplification process" whereby surface events, possibly even cell-to-cell contact, may be related to the control of cell division. Proceeding on the hypothesis that the activity of certain cell surface enzymes may be linked functionally to cytoplasmic structures via microtubule-microfilament (MT-MF) proteins, these studies will investigate the potential interrelationship between the surface- associated enzymes of cyclic nucleotide metabolism (principally protein kinase and adenylate-guanylate cyclases), the MT-MF proteins and the intracellular cyclic nucleotide levels. Since the catalytic activity of adenylate cyclase is dependent on lipid, the effect of altering the fatty acid composition of the membrane lipids on these surface proteins will be investigated. Selective inhibition of the surface-bound protein kinase (with antibodies directed against protein kinase or by use of the protein kinase inhibitor protein) may provide insight into the functional relationship between this enzyme, the adenylate-guanylate cyclases and the MT-MF proteins. In addition, further characterization of the phosphorylatable surface proteins may provide a useful probe for exploring a possible link between surface-associated events and cytoplasmic structures. These studies will be carried out in (C plus) primary mammary epithelial tumor cell cultures and normal and feline sarcoma virus (FeSV) transformed fibroblasts. On the basis of work already accomplished, these objectives are a logical continuation of studies currently in progress and should contribute significantly to our understanding of several dynamic and functional parameters associated with growth control and cell proliferation.